The role of Ca2+ in the regulation of biological processes is prominently expressed in muscle, where activation is produced by a transient elevation of the myoplasmic Ca2+, followed by a reduction that brings about relaxation. This Program Project is concerned with the control of contractile activation by calcium ion in cardiac and skeletal muscle, with emphasis on the role of membranes producing Ca2+ concentration transients in the myoplasm. This renewal application includes four Component Projects, and two Component Core Units. Project 0002 (Inesi) is devoted to studies of molecular structure and function in the Ca2+ transport ATPase of sarcoplasmic reticulum; the aim is to clarify the molecular mechanism whereby catalytic and transport activities are coupled in this protein. Project 0007 (Fambrough-Kessler) is directed to genetic elucidation of structures and functions involved int he expression and regulation of Ca2+ ATPases in cardiac muscle, skeletal muscle, and other tissues. Project 0009 (Rogers-Lederer) deals specifically with Ca2+ transients in cardiac myocytes, and the involvement of protein kinase C in regulation of Ca2+ fluxes and contractile activation; it will also identify the substrates of protein kinase C, and follow the expression of isoforms of this kinase. Core 9001 will provide technical support in the fields of protein chemistry and molecular biology.